Dr.Ashraf Abdelfatah Deyab
Assisstant Professor of Pathology
Faculty of Medicine
Almajma’ah University

Pathology of pulmonary vascular disease
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Damage to the vessels wall:
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- Arteritis with ischaemia and local necrosis
( Wegener's granulomatosis, Churg-Strauss syndrome)
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- Good pasture's syndrome (with circulating antiglomerular basement membrane antibody).
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Obstruction: Thrombo-embolism .
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Variation in intra-vsacular pressure:
Arterial or venous hypertension.

Pathology of Pulmonary hypertension
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The pulmonary circulation is normally one of low resistance.
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Pulmonary BP is normally only about one eighth = (1\8) of systemic BP .
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Pulmonary hypertension (PH) defined when mean pulmonary artery pressure reaches one fourth= (1\4) of systemic levels or greater than BP> 25 mm Hg at rest & greater > 30 mm Hg during exercise.

500 to 600 cases diagnosed annually.
- Occur in men, women and children of all ages,
However most common in women (20-40ys).
- Rare in children but sometimes seen in infants born with heart defect

The pressure within the pulmonary arterial system may be increased for two reasons:
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1) Increased blood flow
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2) Increased resistance within the pulmonary circulation.

Pulmonary hypertension – PH
(Etiology)
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Can be classified into three main
causes:
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1Secondary pulmonary hypertension.
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2- Primary pulmonary hypertension.
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3- Idiopathic.

I)
Pulmonary hypertension – PH
(Etiology)
Secondary pulmonary hypertension :
• Secondary to another medical problem e.g:
• Diseases that impedes flow of blood through
Lungs or
• Diseases that affect the oxygen levels (periods of low oxygen) in blood.
• Examples: COPD, Scleroderma, pulmonary fibrosis, lung diseases such as asbestosis

Pulmonary hypertension – PH
(Etiology)
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Secondary pulmonary hypertension main causes :
1) Cardiac diseases \causes.
2) Recurrent thrombo-embolism .
3) Inflammatory vascular disease.
4) Connective tissue disease
5) Lung diseases

Pulmonary hypertension – PH
(Etiology)
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Secondary pulmonary hypertension :
1) Cardiac diseases :
Congenital or acquired heart disease :
MI- increase left atrial pressure.
- Left to right shunts e.g. septal defects.
Mechanical obstruction e.g. atrial myxoma and mitral stenosis.

Pulmonary hypertension – PH
(Etiology)
2) Recurrent thromboemboli:
3) Inflammatory vascular diseases :
-
.
4) Lung & Connective tissue diseases:
COBD or interstitial, restrictive lung: hypoxia, alveolar and vascular bed damage- increase resistance- increase PH.
- Pneumoconiosis e.g. asbestosis & silicosis.

2- Primary pulmonary hypertension
(Familial) Rare, autosomal dominant.
- Mutations in signaling pathway (BMPR2).
No underlying cause for the high BP in lungs
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- Due to spasm of the muscle layer in pulmonary arteries, patients are sensitive to vasoconstrictors elements.
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3) Idiopathic PH: Sporadic, requires exclusion of other known causes.
Usually women 20-40 years old, some children .

Abnormally high BP in pulmonary vessels arteries
Increased pressure damages large and small pulmonary arteries
Blood vessel walls thicken
Cannot transfer oxygen and carbon dioxide normally
Levels of oxygen in blood fall
Constriction of pulmonary arteries
Further increase in pressure in pulmonary circulation

Pulmonary Hypertension right side of heart must work harder push blood through pulmonary arteries to lungs cor pulmonale right ventricle thickens and enlarges
Heart Failure
In some people, the bone marrow will produce more red blood cells to compensate for less of oxygen in blood leading
Polycythemia
Extra RBCs cause the blood to become thicker and stickier, further increasing the load on the heart
Pulmonary Embolism

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I. Molecular basis (Mutation).
(Primary PH).
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II. Shear and mechanical injury
(Secondary PH)
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III. Pulmonary vasoconstriction
(Secondary PH)
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IV. Idiopathic

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I. Molecular basis (Mutation):
(Familial or primary PH) is caused by mutations in the bone morphogenetic protein receptor type 2
existence and support of
Pulmonary vascular thickening& occlusion : proliferation of endothelial, smooth muscle, and intimal cells accompanied by concentric laminar intimal fibrosis .

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BMPR2 is a cell surface protein belonging to the TGF-β receptor
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BMPR2 specific effects in vascular smooth muscle cells
inhibition
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BMPR2 Mutation lead to increased smooth muscle survival and proliferation may be expected.
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BMPR2 plays it’s effect by support of gene modifier& environmental trigger.

(II) Increased shear and mechanical injury
(Secondary PH) produced endothelial cell dysfunction e.g.: :
Left to-right shunts (Mechanical).
- Thromboembolism, injury mediated by biochemical injury produced by fibrin.

Pulmonary Hypertension
1 .
Pulmonary Arterial
Hypertension 3.
Chronic
Hypoxemia
2. Left Heart
Disease
.
4
4.
Thromboembolic 5. Miscelaneous
-Sarcoid, fibrosing mediastinitis

•
III) Pulmonary vasoconstriction:
Decreased elaboration of prostacyclin& nitric oxide-and increased release of endothelin- this lead to activate platelet Aggregation& adhesion.
* Endothelial activation , makes endothelial cells thrombogenic and promotes the persistence of fibrin.

3) Production and release of growth factors and cytokines induce the migration and replication of vascular smooth muscle cells and elaboration of extracellular matrix.
4) Vasospastic component, after ingestion of certain plants or medicines

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Atheromas, Atheromatous deposits of pulmonary artery, branches.
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Medial hypertrophy = muscular thickness of muscular and elastic arteries.
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Initimal fibrosis= narrowing of the lumen,
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Organizing or recanalized thrombi , with coexistence of diffuse pulmonary
fibrosis this favors recurrence.

Pulmonary hypertension, reveal atheroma formation, usually limited to large vessels

Small peripheral pulmonary artery thromboembolus &their direct role in PH

Vascular changes in pulmonary hypertension
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Marked medial hyperatrophy
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Alveolar haemorrhages

- Plexiform lesion caused by:
- Longstanding severe primary PH and idiopathic& CHD with left-to-right shift .
- Characterized by multi-channeled outpouching of the arterial wall due to reparative lesions in areas of fibrinoid necrosis.

Plexiform lesion- Pulmonary hypertension

Coexistence morphological features:
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Diffuse pulmonary fibrosis , or severe emphysema and chronic bronchitis .
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Dilated vessels and arteritis may also be present.
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Extensive occlusion of the veins by fibrous tissue.

PH Clinical features
Signs & symptoms
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Like other forms of HTN are subtle in the early stages.
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Sign& symptoms are hidden by underlying diseases, and varying from pt. to pt.
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Initial Symptoms : dyspnea, fatigue, chest angina-like pain, cough, fail to put on wei ght like a normal child with slowed growth (in child)
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Overtime Severe respiratory distress , cyanosis , and right ventricular hypertrophy.

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Diagnosis :
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Proper medical work-up& correlation, ruleout others, Echo, lung FT, Lung scan, ect..
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PH outcome:
Death from decompensated cor pulmonale, often with superimposed thromboembolism and pneumonia, usually ensues within 2 to
5 years in 80% of patients.